Unveiling Cu Nanoparticles Formed During Li Deposition in Anode-Free Batteries.

Developing high-energy-density Li metal batteries is essential for sustainable progress, necessitating in-depth studies of complex battery reactions. The presence of metallic Cu impurities detrimentally impacts battery performance, leading to issues such as self-discharging and internal soft short-circuit. Nevertheless, their formation mechanism and structural characteristics have not been revealed clearly. Here the formation of single-crystalline Cu nanoparticles during the Li deposition process in anode-free cells was identified by transmission electron microscopy. Through investigation of the chemical state of Cu before and after Li deposition, the formation of Cu NPs was attributed to the reduction of the oxide layers formed on the surface of Cu current collectors. Additionally, it was observed that Cu nanoparticles can be formed inside of deposited Li metal. This work reveals the formation pathway and microstructural characteristics of Cu nanoparticles appearing during Li deposition, underscoring the importance of nanoscale investigations into the underlying battery reactions.

Comprehensive analysis of clinicopathological characteristics in oral squamous cell carcinoma arising from oral submucous fibrosis: a retrospective study.

BACKGROUND: Oral squamous cell carcinoma arising from oral submucous fibrosis is recognized as a clinicopathologically distinct disease. This study aims to summarize and compare the population and clinicopathologic characteristics of OSCC-OSF with other OSCC in Hunan Province, China. The objective is to formulate treatment strategies more in line with regional characteristics. METHODS: A retrospective review of OSCC cases recruited from the Second Xiangya Hospital from 2010 to 2020 was conducted. A total of 1,413 OSCC patients were selected, including 481 patients with OSCC-OSF and 932 were other OSCC. Population characteristics, risk factors and clinicopathological manifestations were explored in OSCC-OSF and other OSCC, as well as thinprep cytologic test and DNA quantification. RESULTS: We found that OSCC-OSF patients were younger than those with other OSCC. Both types of disease were predominantly observed in males compared to females. Tumor biopsy analysis indicated that tumor cells within OSCC-OSF patients were more likely to be well differentiated and showed a higher frequency of lymph node metastases. Clinicopathological factors, such as the chewing betel nuts habit and smoking, were more prevalent in OSCC-OSF patients in contrast to other OSCC. DNA quantification revealed that the number of DNA aneuploid cells was higher in OSCC-OSF compared to other OSCCs. CONCLUSION: In this study, OSCC-OSF is considered a clinicopathologically distinct disease. Compared with other OSCC, OSCC-OSF patients have a higher incidence of nodal metastases, an early clinical TNM stage, and a lower three-year survival rate. Therefore, early diagnosis and treatment are crucial to improving the prognosis of OSCC-OSF.

A novel biomarker GATM suppresses proliferation and malignancy of cholangiocarcinoma cells by modulating the JNK/c-Jun signalling pathways.

Background: Cholangiocarcinoma (CCA) is the second most common primary malignancy of the liver and is associated with poor prognosis. Despite the emerging role of glycine amidinotransferase (GATM) in cancer development, its function in CCA remains elusive. This study investigated the biological significance and molecular mechanisms of GATM in CCA. Method: GATM expression was measured using immunohistochemistry and western blotting. Cell proliferation, migration, and invasion were assessed through CCK-8, EdU, clone formation, wound healing, and Transwell assays. Rescue experiments were performed to determine whether the JNK/c-Jun pathway is involved in GATM-mediated CCA development. Immunoprecipitation and mass spectrometry were performed to screen for proteins that interact with GATM. The role of GATM in vivo was investigated according to the xenograft experiment. Result: GATM expression was downregulated in CCA tissues and cells (p < 0.05) and had a significant suppressive effect on CCA cell proliferation, migration, and invasion in vitro as well as on tumour growth in vivo (p < 0.05); conversely, GATM knockdown promoted these phenotypes (p < 0.05). Notably, GATM inhibited the JNK/c-Jun pathway, and JNK activation abrogated GATM's antitumor effects (p < 0.05). Isocitrate dehydrogenase 1 (IDH1) interacts with GATM, and IDH1 knockdown significantly attenuated GATM protein degradation. Overexpression of IDH1 restored the biological function of CCA by reversing the inhibition of JNK/c-Jun pathway phosphorylation by GATM (p < 0.05). Conclusion: GATM acts as a tumour suppressor in CCA by regulating the phosphorylation of the JNK/c-Jun pathway. IDH1 interacted with GATM to regulate CCA progression.

Quality of life of family caregivers of children and young adults with Down syndrome: A systematic review and meta-analysis.

Introduction: The aims of this systematic review and meta-analysis are to synthesise quality of life (QOL) of family caregivers of children and young adults with Down syndrome (DS) and determine factors affecting their QOL. Method: This review was conducted as per Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline. Key search terms were "quality of life", "down syndrome" and "trisomy 21". Meta-analysis using random effect model was conducted where feasible. All studies underwent qualitative synthesis. The study protocol was registered with PROSPERO (CRD42023413532). Results: Eighteen studies with 1956 caregivers were included. Of the 10 studies utilising the World Health Organization Quality of Life Instrument-Brief Version, 5 were included in the meta-analysis. Psychosocial domain had the highest score with mean (95% confidence interval [CI]) of 63.18 (39.10-87.25). Scores were poorer in physical, environmental and social domains: 59.36 (28.24-90.48), 59.82 (19.57-100.07) and 59.83 (44.24-75.41), respectively. Studies were heterogenous with I2 values ranging from 99-100% (P<0.01). The remaining 8 studies used 6 other instruments. Qualitative synthesis revealed that caregivers' QOL was adversely affected by child-related factors, such as level of functional independence, developmental delay, presence of multiple comorbidities, impaired activities of daily living and poor sleep quality. Environmental factors that adversely affected caregivers' QOL included number of children, housing and support from the family. Personal factors that affected caregivers' QOL included age, being a single mother, low education and low income. Conclusion: QOL of caregivers of children with DS was lower than population reference data. Understand-ing the factors that influence family caregivers' QOL is an essential step towards improving the QOL of caregivers and their children with DS.

Quality of life of children and young adults with Down syndrome from caregivers' perspective: A systematic review and meta-analysis.

Introduction: Down syndrome (DS) negatively impacts the well-being of affected individuals. This study aimed to summarise the evidence on quality of life (QOL) of children and young adults with DS using quantitative measures from caregivers' perspective and identify factors that affected their QOL. Method: Database search was conducted on PubMed, Embase, Web of Science and CINAHL on 24 April 2024. Meta-analysis using random effects model was conducted where feasible. All studies underwent qualitative synthesis. The study protocol was registered with PROSPERO (CRD42023413532). Results: Seventeen studies involving 3038 children with DS using various QOL measures were included: Pediatric Quality of Life Inventory (PedsQL) (8 studies), KIDSCREEN (4 studies), KidsLife (2 studies), The Netherlands Organization for Applied Scientific Research Academic Medical Center Children's QOL (2 studies) and Personal Outcome Scale (1 study). Meta-analysis on PedsQL studies compared scores between children with DS and typically developing (TD) children. Total scale score was lower in children with DS (mean 70.28, 95% confidence interval [CI] 64.31-76.24) compared to TD children (mean 88.17, 95% CI 80.50-95.83). All subdomains of PedsQL were also lower in children with DS. Within the domain of psychosocial health, children with DS had statistically significant lower social functioning (standardised mean difference -1.40, 95% CI -2.27 to -0.53) and school functioning (standardised mean difference -1.09, 95% CI -1.55 to -0.62) scores, but similar emotional functioning scores. Qualitative synthesis revealed poorer subdomain QOL compared to TD children, especially in social functioning and cognitive functioning. QOL worsened during adolescent years. Family variables (parental education and occupation) did not affect parental perception of children's QOL. Children with DS who had higher intelligent quotient had better QOL. Conclusion: Children with DS have lower caregiver-reported QOL than TD children, especially in social functioning and school functioning subdomains.

Radical-triggered translocation of C-C double bond and functional group.

Multi-site functionalization of molecules provides a potent approach to accessing intricate compounds. However, simultaneous functionalization of the reactive site and the inert remote C(sp3)-H poses a formidable challenge, as chemical reactions conventionally occur at the most active site. In addition, achieving precise control over site selectivity for remote C(sp3)-H activation presents an additional hurdle. Here we report an alternative modular method for alkene difunctionalization, encompassing radical-triggered translocation of functional groups and remote C(sp3)-H desaturation via photo/cobalt dual catalysis. By systematically combining radical addition, functional group migration and cobalt-promoted hydrogen atom transfer, we successfully effectuate the translocation of the carbon-carbon double bond and another functional group with precise site selectivity and remarkable E/Z selectivity. This redox-neutral approach shows good compatibility with diverse fluoroalkyl and sulfonyl radical precursors, enabling the migration of benzoyloxy, acetoxy, formyl, cyano and heteroaryl groups. This protocol offers a resolution for the simultaneous transformation of manifold sites.

Early growth response 1 exacerbates thoracic aortic aneurysm and dissection of mice by inducing the phenotypic switching of vascular smooth muscle cell through the activation of Krüppel-like factor 5.

AIM: Vascular smooth muscle cell (VSMC) phenotypic switching has been reported to regulate vascular function and thoracic aortic aneurysm and dissection (TAAD) progression. Early growth response 1 (Egr1) is associated with the differentiation of VSMCs. However, the mechanisms through which Egr1 participates in the regulation of VSMCs and progression of TAAD remain unknown. This study aimed to investigate the role of Egr1 in the phenotypic switching of VSMCs and the development of TAAD. METHODS: Wild-type C57BL/6 and SMC-specific Egr1-knockout mice were used as experimental subjects and fed ß-aminopropionitrile for 4 weeks to construct the TAAD model. Ultrasound and aortic staining were performed to examine the pathological features in thoracic aortic tissues. Transwell, wound healing, CCK8, and immunofluorescence assays detected the migration and proliferation of synthetic VSMCs. Egr1 was directly bound to the promoter of Krüppel-like factor 5 (KLF5) and promoted the expression of KLF5, which was validated by JASPAR database and dual-luciferase reporter assay. RESULTS: Egr1 expression increased and was partially co-located with VSMCs in aortic tissues of mice with TAAD. SMC-specific Egr1 deficiency alleviated TAAD and inhibited the phenotypic switching of VSMC. Egr1 knockdown prevented the phenotypic switching of VSMCs and subsequently suppressed the migration and proliferation of synthetic VSMCs. The inhibitory effects of Egr1 deficiency on VSMCs were blunted once KLF5 was overexpressed. CONCLUSION: Egr1 aggravated the development of TAAD by promoting the phenotypic switching of VSMCs via enhancing the transcriptional activation of KLF5. These results suggest that inhibition of SMC-specific Egr1 expression is a promising therapy for TAAD.

Retrospective Analysis of Radiofrequency Ablation in Patients with Small Solitary Hepatocellular Carcinoma: Survival Outcomes and Development of a Machine Learning Prognostic Model.

BACKGROUND AND OBJECTIVE: The effectiveness of radiofrequency ablation (RFA) in improving long-term survival outcomes for patients with a solitary hepatocellular carcinoma (HCC) measuring 5 cm or less remains uncertain. This study was designed to elucidate the impact of RFA therapy on the survival outcomes of these patients and to construct a prognostic model for patients following RFA. METHODS: This study was performed using the Surveillance, Epidemiology, and End Results (SEER) database from 2004 to 2017, focusing on patients diagnosed with a solitary HCC lesion ≤5 cm in size. We compared the overall survival (OS) and cancer-specific survival (CSS) rates of these patients with those of patients who received hepatectomy, radiotherapy, or chemotherapy or who were part of a blank control group. To enhance the reliability of our findings, we employed stabilized inverse probability treatment weighting (sIPTW) and stratified analyses. Additionally, we conducted a Cox regression analysis to identify prognostic factors. XGBoost models were developed to predict 1-, 3-, and 5-year CSS. The XGBoost models were evaluated via receiver operating characteristic (ROC) curves, calibration plots, decision curve analysis (DCA) curves and so on. RESULTS: Regardless of whether the data were unadjusted or adjusted for the use of sIPTWs, the 5-year OS (46.7%) and CSS (58.9%) rates were greater in the RFA group than in the radiotherapy (27.1%/35.8%), chemotherapy (32.9%/43.7%), and blank control (18.6%/30.7%) groups, but these rates were lower than those in the hepatectomy group (69.4%/78.9%). Stratified analysis based on age and cirrhosis status revealed that RFA and hepatectomy yielded similar OS and CSS outcomes for patients with cirrhosis aged over 65 years. Age, race, marital status, grade, cirrhosis status, tumor size, and AFP level were selected to construct the XGBoost models based on the training cohort. The areas under the curve (AUCs) for 1, 3, and 5 years in the validation cohort were 0.88, 0.81, and 0.79, respectively. Calibration plots further demonstrated the consistency between the predicted and actual values in both the training and validation cohorts. CONCLUSION: RFA can improve the survival of patients diagnosed with a solitary HCC lesion ≤5 cm. In certain clinical scenarios, RFA achieves survival outcomes comparable to those of hepatectomy. The XGBoost models developed in this study performed admirably in predicting the CSS of patients with solitary HCC tumors smaller than 5 cm following RFA.

Phosphate modified nanoarchitectonics for promoted photocatalytic singlet oxygen generation and carbamazepine degradation of (010) facet-exposed BiOCl.

1O2 generation over (001) or (010) facet exposed BiOCl (B001 or B010) with/without phosphate modification were studied from the aspects of excitons involved energy transfer route, the O2- oxidation based charge transfer route and the H2O2 oxidation by HClO. Phosphate modification not only enhance charge separation thus result in H2O2 oxidation by HClO to release 1O2 but also weaken excitonic effect in the confined layer of BiOCl accordingly affect 1O2 generation via energy transfer. Considering [001] orientation favors the formation of excitons than that of [010] direction over BiOCl, excitons loss was hardly compensated by the H2O2 oxidation by HClO for 1O2 generation over phosphate modified B001. Nevertheless, limited excitonic effect makes the O2- oxidation by h+ via charge transfer as dominant route for 1O2 yielding over B010, the extra H2O2 oxidation with HClO after phosphate modification significantly enhance 1O2 generation over B010 followed with 2.2 times higher carbamazepine photodegradation activity. The initial attack of CC bond via 1O2 to form epoxide played important roles on carbamazepine degradation. This study demonstrated that the facet-specific phosphate modification of photocatalysts can finely tune reactive 1O2 species for superior pharmaceuticals degradations.

Deterministic Synthesis of a Two-Dimensional MAPbI3 Nanosheet and Twisted Structure with Moiré Superlattice.

The synthesis of extremely thin 2D halide perovskites and the exploration of their interlayer interactions have garnered significant attention in current research. A recent advancement we have made involves the development of a successful technique for generating ultrathin MAPbI3 nanosheets with controlled thickness and an exposed intrinsic surface. This innovative method relies on utilizing the Ruddlesden-Popper (RP) phase perovskite (BA2MAn-1PbnI3n+1) as a template. However, the precise reaction mechanism remains incompletely understood. In this work, we systematically examined the dynamic evolution of the phase conversion process, with a specific focus on the influence of inorganic slab (composed of [PbI6]4- octahedrons) numbers on regulating the thickness and quality of the resulting MAPbI3 nanosheets. Additionally, the atomic structure is directly visualized using the transmission electron microscopy (TEM) method, confirming its exceptional quality. To illustrate interfacial interactions in ultrathin structures, artificial moiré superlattices are constructed through a physical transfer approach, revealing multiple localized high-symmetry stacks within a distinctive square moiré pattern. These findings establish a novel framework for investigating the physics of interfacial interactions in ionic semiconducting crystals.

High-performance Complementary Electrochromic Batteries using Nb18W16O93 by the Synergistic Effects of Aqueous Al3+/K+ Dual-ion.

Multivalent ions, especially Al3+ in aqueous electrolyte contributes to higher capacity and color contrast for more sustainable post-lithium electrochromism and energy storages. However, the lack of suitable cathodic and anodic electrochromic materials is a major challenge for Al-ion electrochromic batteries, which limits their optical contrast and lifespan. Herein, we report that Wadsley-Roth phase Nb18W16O93 with open structure achieves Al3+ intercalation/extraction reversibly. The complementary electrochromic energy storage devices based on Nb18W16O93 coupled with Prussian blue using hybrid Al3+/K+ aqueous electrolytes show a fast response, a high capacity and a large coloring efficiency. The superior performances are due to the cations of Al3+ and K+ selectively insert/extract in the electrode of Nb18W16O93 and Prussian blue, respectively. This work provides an effective strategy for high-performance and low-cost electrochromic batteries with higher sustainability.

Anilines Formation via Molybdenum-Catalyzed Intermolecular Reaction of Ynones with Allylic Amines.

The multi-substituted anilines are widely found in organic synthesis, medicinal chemistry and material science. The quest for robust and efficient methods to construct a diverse array of these compounds using readily accessible starting materials under simple reaction conditions is of utmost importance. Here, we report an unprecedented and efficient approach for the synthesis of 2,4-di and 2,4,6-trisubstituted anilines. With a simple molybdenum(VI) catalyst, a wide range of 2,4-di and 2,4,6-trisubstituted anilines were efficiently prepared in generally good to excellent yields from readily accessible ynones and allylic amines. The synthetic potential of this methodology was further underscored by its applications in several synthetic transformations, gram-scale reactions, and derivatization of bioactive molecules. Preliminary mechanistic studies suggested that this aniline formation might involve a cascade of aza-Michael addition, [1, 6]-proton shift, cyclization, dehydration, 6π-electrocyclization, and aromatization. This novel strategy provided a robust, simple, and modular approach for the syntheses of various valuable di- or trisubstituted anilines, some of which were otherwise challenging to access.

Impact of beta-blocker usage on delirium in patients with sepsis in ICU: a cross-sectional study.

Introduction: Delirium in patients with sepsis can be life-threatening. This study aims to investigate the impact of the use of beta-blockers on the occurrence of delirium in patients with sepsis in the ICU by utilizing a comprehensive dataset. Methods: This is a cross-sectional study conducted using the data obtained from a single ICU in the USA. Patients diagnosed with sepsis and receiving beta-blockers were compared with those not receiving beta-blockers. Propensity score matching (PSM) and multiple regression analysis were employed to adjust for potential confounders. Results: Among the 19,660 patients hospitalized for sepsis, the beta-blocker and non-user groups comprised 13,119 (66.73%) and 6,541 (33.27%) patients, respectively. Multivariable logistic regression models revealed a significant reduction of 60% in 7-day delirium for beta-blocker users (OR = 0.40, 95% CI: 0.37-0.43, p < 0.001), for 30-day delirium (OR = 0.32, 95% CI: 0.29-0.35, p < 0.001), and for 90-day delirium (OR = 0.33, 95% CI: 0.30-0.35, p < 0.001). The PSM results further strengthen the validity of these findings. An analysis of safety issues demonstrated that beta-blockers may have an impact on the risk of acute kidney injury. However, following PSM, the results are not considered robust. Furthermore, there was no discernible change in the odds of renal replacement therapy and the length of ICU stays. Discussion: Our findings suggest a potential protective effect of beta-blockers against delirium in patients with sepsis. Nevertheless, the observational design limits causal inference, necessitating future randomized controlled trials to validate these findings.

Common and differential EEG microstate of major depressive disorder patients with and without response to rTMS treatment.

OBJECTIVE: Repetitive transcranial magnetic stimulation (rTMS) has recently emerged as a novel treatment option for patients with major depressive disorder (MDD), but clinical observations reveal variability in patient's responses to rTMS. Therefore, it is clinically significant to investigate the baseline neuroimaging differences between patients with (Responder) and without (NonResponder) response to rTMS treatment and predict rTMS treatment outcomes based on baseline neuroimaging data. METHOD: Baseline resting-state EEG data and Beck Depression Inventory (BDI) were collected from 74 rTMS Responder, 43 NonResponder, and 47 matched healthy controls (HC). EEG microstate analysis was applied to analyze common and differential microstate characteristics of Responder and NonResponder. In addition, the microstate temporal parameters were sent to four machine learning models to classify Responder from NonResponder. RESULT: There exists some common and differential EEG microstate characteristics for Responder and NonResponder. Specifically, compared to the HC group, both Responder and NonResponder exhibited a significant increase in the occurrence of microstate A. Only Responder showed an increase in the coverage of microstate A, occurrence of microstate D, transition probability (TP) from A to D, D to A, and C to A, and a decrease in the duration of microstates B and E, TP from A to B and C to B compared to HC. Only NonResponder exhibited a significant decrease in the duration of microstate D, TP from C to D, and an increase in the occurrence of microstate E, TP from C to E compared to HC. The primary differences between the Responder and NonResponder are that Responder had higher parameters for microstate D, TP from other microstates to D, and lower parameters for microstate E, TP from other microstates to E compared to NonResponder. Baseline parameters of microstate D showed significant correlation with Beck Depression Inventory (BDI) reduction rate. Additionally, these microstate features were sent to four machine learning models to predict rTMS treatment response and classification results indicate that an excellent predicting performance (accuracy = 97.35 %, precision = 96.31 %, recall = 100 %, F1 score = 98.06 %) was obtained when using AdaBoost model. These results suggest that baseline resting-state EEG microstate parameters could serve as robust indicators for predicting the effectiveness of rTMS treatment. CONCLUSION: This study reveals significant baseline EEG microstate differences between rTMS Responder, NonResponder, and healthy controls. Microstates D and E in baseline EEG can serve as potential biomarkers for predicting rTMS treatment outcomes in MDD patients. These findings may aid in identifying patients likely to respond to rTMS, optimizing treatment plans and reducing trial-and-error approaches in therapy selection.

Efficient generation of human NOTCH ligand-expressing haemogenic endothelial cells as infrastructure for in vitro haematopoiesis and lymphopoiesis.

Arterial endothelial cells (AECs) are the founder cells for intraembryonic haematopoiesis. Here, we report a method for the efficient generation of human haemogenic DLL4+ AECs from pluripotent stem cells (PSC). Time-series single-cell RNA-sequencing reveals the dynamic evolution of haematopoiesis and lymphopoiesis, generating cell types with counterparts present in early human embryos, including stages marked by the pre-haematopoietic stem cell genes MECOM/EVI1, MLLT3 and SPINK2. DLL4+ AECs robustly support lymphoid differentiation, without the requirement for exogenous NOTCH ligands. Using this system, we find IL7 acts as a morphogenic factor determining the fate choice between the T and innate lymphoid lineages and also plays a role in regulating the relative expression level of RAG1. Moreover, we document a developmental pathway by which human RAG1+ lymphoid precursors give rise to the natural killer cell lineage. Our study describes an efficient method for producing lymphoid progenitors, providing insights into their endothelial and haematopoietic ontogeny, and establishing a platform to investigate the development of the human blood system.

Effectiveness of digital intelligence interventions on depression and anxiety in older adults: A systematic review and meta-analysis.

BACKGROUND: Depression and anxiety are common mental disorders in later life. Digital intelligence interventions overcome the limitations of conventional psychotherapy and offer new treatments for depression and anxiety. However, the effectiveness among older adults remains unclear. METHODS: Databases including Pubmed, Web of Science, the Cochrane Library, Medline, CINAHL, PsycINFO, and Embase were searched for Randomized Controlled Trials (RCTs) from inception to November 22, 2023. Statistical analyses were conducted using Stata 18.0 and Review Manager 5.4. RESULTS: The initial search found 9369 papers, with 21 meeting the inclusion criteria (e.g., RCTs involving older adults aged 50 and older that assessed digital intelligence interventions on depression and anxiety symptoms). Meta-analyses revealed that, compared to control groups, digital intelligence interventions significantly reduced depression symptoms (SMD: -0.58; 95 % CI: -0.80, -0.35) and anxiety symptoms (SMD: -0.39; 95 % CI: -0.58, -0.19). Subgroup analysis revealed that internet-based Cognitive Behavioral Therapy (iCBT), interventions lasting 7 to 10 weeks, and the use of the Patient Health Questionnaire (PHQ) and Generalized Anxiety Disorder-7 (GAD-7) scales, especially in other regions, had the most pronounced effects. CONCLUSIONS: Digital intelligence interventions reduce depressive and anxious symptoms in older adults, supporting the development of evidence-based treatment guidelines in the digital era.

The AP-2 Family of Transcription Factors-Still Undervalued Regulators in Gastroenterological Disorders.

Activating enhancer-binding protein 2 (AP-2) is a family of transcription factors (TFs) that play crucial roles in regulating embryonic and oncogenic development. In addition to splice isoforms, five major family members encoded by the TFAP2A/B/C/D/E genes have been identified in humans, i.e., AP-2α/ß/γ/δ/ε. In general, the first three TFs have been studied more thoroughly than AP-2δ or AP-2ε. Currently, there is a relatively limited body of literature focusing on the AP-2 family in the context of gastroenterological research, and a comprehensive overview of the existing knowledge and recommendations for further research directions is lacking. Herein, we have collected available gastroenterological data on AP-2 TFs, discussed the latest medical applications of each family member, and proposed potential future directions. Research on AP-2 in gastrointestinal tumors has predominantly been focused on the two best-described family members, AP-2α and AP-2γ. Surprisingly, research in the past decade has highlighted the importance of AP-2ε in the drug resistance of gastric cancer (GC) and colorectal cancer (CRC). While numerous questions about gastroenterological disorders await elucidation, the available data undoubtedly open avenues for anti-cancer targeted therapy and overcoming chemotherapy resistance. In addition to gastrointestinal cancers, AP-2 family members (primarily AP-2ß and marginally AP-2γ) have been associated with other health issues such as obesity, type 2 diabetes, liver dysfunction, and pseudo-obstruction. On the other hand, AP-2δ has been poorly investigated in gastroenterological disorders, necessitating further research to delineate its role. In conclusion, despite the limited attention given to AP-2 in gastroenterology research, pivotal functions of these transcription factors have started to emerge and warrant further exploration in the future.

RNA-binding protein GIGYF2 orchestrates hepatic insulin resistance through STAU1/PTEN-mediated disruption of the PI3K/AKT signaling cascade.

BACKGROUND: Obesity is well-established as a significant contributor to the development of insulin resistance (IR) and diabetes, partially due to elevated plasma saturated free fatty acids like palmitic acid (PA). Grb10-interacting GYF Protein 2 (GIGYF2), an RNA-binding protein, is widely expressed in various tissues including the liver, and has been implicated in diabetes-induced cognitive impairment. Whereas, its role in obesity-related IR remains uninvestigated. METHODS: In this study, we employed palmitic acid (PA) exposure to establish an in vitro IR model in the human liver cancer cell line HepG2 with high-dose chronic PA treatment. The cells were stained with fluorescent dye 2-NBDG to evaluate cell glucose uptake. The mRNA expression levels of genes were determined by real-time qRT-PCR (RT-qPCR). Western blotting was employed to examine the protein expression levels. The RNA immunoprecipitation (RIP) was used to investigate the binding between protein and mRNA. Lentivirus-mediated gene knockdown and overexpression were employed for gene manipulation. In mice, an IR model induced by a high-fat diet (HFD) was established to validate the role and action mechanisms of GIGYF2 in the modulation of HFD-induced IR in vivo. RESULTS: In hepatocytes, high levels of PA exposure strongly trigger the occurrence of hepatic IR evidenced by reduced glucose uptake and elevated extracellular glucose content, which is remarkably accompanied by up-regulation of GIGYF2. Silencing GIGYF2 ameliorated PA-induced IR and enhanced glucose uptake. Conversely, GIGYF2 overexpression promoted IR, PTEN upregulation, and AKT inactivation. Additionally, PA-induced hepatic IR caused a notable increase in STAU1, which was prevented by depleting GIGYF2. Notably, silencing STAU1 prevented GIGYF2-induced PTEN upregulation, PI3K/AKT pathway inactivation, and IR. STAU1 was found to stabilize PTEN mRNA by binding to its 3'UTR. In liver cells, tocopherol treatment inhibits GIGYF2 expression and mitigates PA-induced IR. In the in vivo mice model, GIGYF2 knockdown and tocopherol administration alleviate high-fat diet (HFD)-induced glucose intolerance and IR, along with the suppression of STAU1/PTEN and restoration of PI3K/AKT signaling. CONCLUSIONS: Our study discloses that GIGYF2 mediates obesity-related IR by disrupting the PI3K/AKT signaling axis through the up-regulation of STAU1/PTEN. Targeting GIGYF2 may offer a potential strategy for treating obesity-related metabolic diseases, including type 2 diabetes.

Exploring Embodied Cognition and Brain Dynamics Under Multi-Tasks Target Detection in Immerse Projector-Based Augmented Reality (IPAR) Scenarios.

Embodied cognition explores the intricate interaction between the brain, body, and the surrounding environment. The advancement of mobile devices, such as immersive interactive computing and wireless electroencephalogram (EEG) devices, has presented new challenges and opportunities for studying embodied cognition. To address how mobile technology within immersive hybrid settings affects embodied cognition, we propose a target detection multitask incorporating mixed body movement interference and an environmental distraction light signal. We aim to investigate human embodied cognition in immersive projector-based augmented reality (IPAR) scenarios using wireless EEG technology. We recruited and engaged fifteen participants in four multitasking conditions: standing without distraction (SND), walking without distraction (WND), standing with distraction (SD), and walking with distraction (WD). We pre-processed the EEG data using Independent Component Analysis (ICA) to isolate brain sources and K-means clustering to categorize Independent Components (ICs). Following that, we conducted time-frequency and correlation analyses to identify neural dynamics changes associated with multitasking. Our findings reveal a decline in behavioral performance during multitasking activities. We also observed decreases in alpha and beta power in the frontal and motor cortex during standing target search tasks, decreases in theta power, and increases in alpha power in the occipital lobe during multitasking. We also noted perturbations in theta band power during distraction tasks. Notably, physical movement induced more significant fluctuations in the frontal and motor cortex than distractions from social environment light signals. Particularly in scenarios involving walking and multitasking, there was a noticeable reduction in beta suppression. Our study underscores the importance of brain-body collaboration in multitasking scenarios, where the simultaneous engagement of the body and brain in complex tasks highlights the dynamic nature of cognitive processes within the framework of embodied cognition. Furthermore, integrating immersive augmented reality technology into embodied cognition research enhances our understanding of the interplay between the body, environment, and cognitive functions, with profound implications for advancing human-computer interaction and elucidating cognitive dynamics in multitasking.

XMEN-associated Systemic EBV-positive T-cell Lymphoma of Childhood: Report of Two Cases and Literature Review.

X-linked immunodeficiency with magnesium defect, Epstein-Barr virus (EBV) infection, and neoplasia (XMEN) is an extremely rare inborn error of immunity (IEI) caused by X-linked recessive inheritance and loss-of-function mutations in the MAGT1 gene, resulting in magnesium ion channel defects. This article reports 2 cases of systemic EBV-positive T-cell Lymphoma of childhood (SETLC) associated with XMEN, which have not been reported before. Whole exome sequencing (WES) in their family revealed previously unreported MAGT1 gene mutations (c.77T>C, p.I26T; c.956-957del: p.Ser319Tyrfs) inherited from their mothers. These mutations expand the spectrum of gene mutations in XMEN disease. The importance of genetic testing for MAGT1 mutations in the initial diagnosis of SETLC was emphasized. We also review the literature on this uncommon IEI.